Is AHI1 p.Pro402fs (c.1205del) pathogenic?

AHI1 p.Pro402fs (c.1205del) is classified Pathogenic/Likely pathogenic in AHI1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-31). Very rare (popmax 0.00172%, amr); Associated with Joubert syndrome 1.

What condition is associated with AHI1 p.Pro402fs (c.1205del)?

AHI1 p.Pro402fs (c.1205del) is associated with Joubert syndrome 1, Joubert syndrome (ClinVar).

How common is AHI1 p.Pro402fs (c.1205del) in the general population?

AHI1 p.Pro402fs (c.1205del) is very rare (popmax 0.00172%, amr) (gnomAD).

AHI1 p.Pro402fs

c.1205del · rs794729195 · VCV202167

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00172%, amr)

Conditions

Joubert syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 0.026, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00172% Admixed American · 1/58,264 alleles

Overall 0.000189% 3/1,586,186 alleles · very rare exomes 3/1,433,836 · genomes 0/152,350 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00172%	58,264
Remaining individualsnot grpmax-eligible	0.00163%	61,290
South Asian	0.00115%	86,656

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AHI1
Protein: p.Pro402fs
Coding: c.1205del
MANE Select: NM_001134831
dbSNP: rs794729195
Type: Deletion
Location: chr6:135455873 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.03 · 1 PDB
Residue 402: the 'interaction with hap1' region

Full AHI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome

Similar variants

AHI1 p.Asn686fs Pathogenic ★★ same condition
AHI1 p.Asp65fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Cys751fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Glu1158fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Glu144fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Glu178fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Ile474fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Lys34fs Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ahi1-p-pro402fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown